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PubMedDate not supplied

The AAS, ICP-MS and electrochemical determinations of zinc in selected pharmaceutical preparations.

Controlling of elements content in drugs is indispensable for drug quality evaluation. Zinc was selected for study because zinc contents in drugs span a wide range. Numerous multi-mineral preparations used and nutritional supplements to make up for the microelemental deficiencies in humans and animals, contain less than 0.001% zinc, i.e., trace amounts of zinc. On the other hand, external application drugs such as ointments and suppositories usually contain more than 0.1% of zinc. Zinc was determined out in Technilab's "Hemacort HC" ointments and suppositories, in Nattermann's "Dolovit Multimineral" tablets, and in Richter Pharma's "Minerasol" parenteral veterinary solution. These preparations were selected for investigation not only in view of differentiated zinc contents, but also because of the various drug forms and various procedures involved in sample preparation procedures. The tablets were dissolved with the aid of microwave energy, the ointment and suppositories were extracted, and the parenteral solution was diluted with water or with and aqueous 1% nitric acid. Atomic absorption spectrometry with graphite-tube (AAS), inductively coupled plasma mass spectrometry (ICP-MS), adsorptive stripping voltammetry (AdSV), square-wave voltammetry (SWV), and differential pulse polarography (DPP) were used for the determinations. Zinc was determined within concentration ranges of 20-40 ppb, 0.5-20 ppb, and 10-50 ppb by AAS, ICP-MS and AdSV, respectively. In the AAS and ICP-MS, zinc recoveries were contained within the limits of 101.8-114.2% and 111.0-114.2% respectively. The errors of determination (RSD) were 3.37-5.74% in AAS, 0.28-4.47% in ICP-MS and 0.19-2.50% in the electrochemical method.

Calibration↗

PubMed1975

Data on the metabolism of benzylisoquinoline derivatives. The metabolism of drotaverin.

Studying the metabolism of drotaverin (No-Spa¿), we have elaborated a method for the isolation, purification and separation of metabolites and of drotaverin excreted in unchanged form in the urine and feces. The structure of the chief metabolites was cleared by t.l.c., polarography, UV spectrophotometry, and mass spectrometry. It was stated that beside drotaverin excreted in unchanged form, the biotransformation of the molecule results in the formation of oxidation and desalkylation products.

Animals↗

PubMed1975

Reactive hyperaemia in the hind limbs of rabbits. II. The effect of changes in oxygen tension and temperature.

The effect on reactive hyperaemia of variations in oxygen content of the inspired air and in tissue temperature, was studied by electromagnetic flowmetry in the hind limbs of rabbits. Flowmetry was used together with oxygen polarography to compare recovery time of blood flow and recovery time of oxygen tension in muscle tissue during reactive hyperaemia. After occlusions lasting more than 10 seconds; recovery time of oxygen tension was much shorter than recovery time of blood flow. Breathing of different oxygen concentrations induced relatively small changes of reactive hyperaemia. After increasing tissue temperature all variables of reactive hyperaemia were reduced following 10-60 seconds' occlusion. On the other hand, after 5 minutes' occlusion percentual repayment and recovery time increased significantly. During hypothermia, percentual repayment and recovery time were reduced significantly after 5 minutes' occlusion. Thus, the time-response curves for percentual repayment and recovery time during hyper-and hypothermia crossed each other when occlusion time was extended beyond 60 seconds. Normalization of oxygen tension when blood flow was still increased seems to exclude that oxygen deficiency per se is the only cause of reactive hyperaemia. Oxygen deficiency may be a contributory factor in the initiation of vasodilation during circulatory arrest and may possibly be of importance in the first part of reactive hyperaemia. The results of changing the tissue temperature suggested that metabolites which are accumulated during circulatory arrest, maintain the increased blood flow, at least after release of longer occlusions.

Animals↗

PubMed2001

[Role of mitochondrial lesion in pathogenesis of sporadic rett syndrome].

OBJECTIVE: To investigate the role of mitochondrial lesion in children with Rett syndrome (RTT). METHODS: The platelets from 6 cases with Rett syndrome and 9 normal controls were fused with mitochondrial DNA-lacking rho degrees cell by polyethylene glycol-mediated fusion technique. The oxygen free radical was evaluated by the polarography with substrates of vitamine C and TMPD (N, N, N', N'-tetramethyl-p-phenlene diamine). The rate of apoptosis was determinated by flow cytometry. The apoptosis was observed by electronic microscope and TUNEL method. The t test between groups was adopted in study. RESULTS: In RTT patients, the anticyano-respiration significantly increased by 23% (t = 4.76, P < 0.01). After 6-hour coincubation with 100 micromol/L H(2)O(2), the rate of apoptosis is (3.6 +/- 1.1) % in normal control, and (9.9 +/- 2.7) % in RTT group with significant difference (t = 6.30, P < 0.01), the existence of apoptosis was confirmed by electronic microscope and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL). CONCLUSION: After mitochondrial DNA transfer, the oxygen free radical increased in mitochondrial respiratory chain in cybrids of RTT children. RTT cybrid cell lines demonstrated an increased sensitivity to H(2)O(2)-induced apoptotic cell death as compared to control cybrids. The mitochondrial lesion might play a role in the pathogenesis of Rett syndrome.

Apoptosis↗

PubMedDate not supplied

[Effects of trimetazidine on altered functions of rat kidney induced by cyclosporine].

A mitochondrial dysfunction has been suggested to explain chronic renal toxicity observed in ciclosporine A therapy. Our study has investigated whether trimetazidine allows inhibition of mitochondrial alteration induced by ciclosporine A. Oxidative phosphorylation was measured by polarography, calcium fluxes by a specific calcium electrode and the mitochondrial swelling by determination of the optical density at 520 nm, using a spectrophotometer. The ciclosporine A effect on the respiratory control was fully inhibited by trimetazidine (EC50 5.10 x 10(-7) M; Emax 11 per cent). Trimetazidine also inhibited the ciclosporine effects on calcium fluxes, i.e. calcium accumulation into the matrix and delay of efflux. Trimetazidine allows a decrease of mitochondrial dysfunction induced by ciclosporine A.

Animals↗

PubMed1967

Exobiology and the effect of physical factors on micro-organisms.

A study of the action of different physical factors on micro-organisms is necessary for a further development of exobiology. The action of temperature on crystalline preparations of catalase and peroxidase was studied by means of oscillographic polarography. A determination of the height of polarographic waves at the decrease of temperature from 20 degrees C to 0 degrees C has shown that structural elements of the peroxidase molecule connected with the enzymatic activity are more stable with the decrease of temperature cf. catalase. A relative resistance of the dehydrogenase activity in Az. vinelandii cells to high vacuum was found. Incubation of azotobacter cells under vacuum of 10(-9) mm Hg during 72 hr did not decrease the activity of alcohol and succinic dehydrogenase. Bac. cereus spores can be preserved from bactericidal UV action by thin films of chrome. The thickness of chrome film being 200-670 angstroms, spores are killed by a dose of 7.8 x 10(7) erg/cm2 at 253.7 microns wave length. Spores covered by chrome film thicker than 800 angstroms remain alive after this treatment. Investigations carried out with an 'Artificial Mars' camera led to the following results. The growth of Bac. megaterium on liquid growth media in this camera ceases as a result of UV rays killing all cells after 3 weeks. Untreated bacteria grow in the camera for a long time. Spore-forming bacteria isolated from the sand of the Kara-Kum Desert grow in ground limonite (with the addition of 2% garden soil) having maximum hygroscopic humidity (3.8%). Freezing and thawing (from -60 degrees C to +25 degrees C) corresponding to day temperature deviations on Mars, low pressure (P=10 mm Hg) and the composition of the atmosphere (CO2-50%, N2-40%, Ar-10%) do not influence the growth of xerophylic bacteria under study. Humidity is the main factor limiting the growth of micro-organisms under 'Artificial Mars' conditions. According to the further development of the microbiological meteorite analysis methods, samples of rocks and stone meteorites were sterilized, incubated in the desert or on a snow surface in the Arctic and after different times (from 100 days to 7 months), investigated. In all cases, microbes were found only on the sample surfaces, whereas 1 cm from the surface and in the central parts micro-organism were completely absent. Hence, microbiological analysis of central parts of meteorites fallen in the Arctic or during dry periods of the year in the desert can give reliable results.

Alcohol Dehydrogenase↗

PubMedDate not supplied

On lead(II) glycocholate solubility.

The solubility of lead(II) glycocholate was studied as a function of glycocholate ion concentration at 25 degrees C and in 0.100, 0.500 and 0.800 mol dm-3 N(CH3)4Cl as a constant ionic medium. For this purpose the total concentration of lead(II) was determined by means of atomic absorption spectrophotometry and polarography measurements in solution equilibrated with solid lead(II) glycocholate at known hydrogen ion concentration. The free concentration of lead(II) and hydrogen ions was determined by measuring the electromotive force(e.m.f.) of galvanic cells involving lead amalgam and glass electrode. The e.m.f. measurements were carried out both in clear solutions before precipitation and in the presence of the precipitate. The results of the solubility and e.m.f. measurements could be explained by assuming the presence of associated species between lead(II) and glycocholate. The solubility product and the association constants were determined for all the ionic medium concentrations.

Glycocholic Acid↗

PubMed2002

The impact of aging on vasa nervorum, nerve blood flow and vasopressin responsiveness.

OBJECTIVE: Aging impacts microvessels in a number of tissue beds. Vasopressin acts as a vasoconstrictor in most blood vessels but may also cause vasodilation. We evaluated the role of aging and vasopressin in the regulation of nerve blood flow (NBF) in rat peripheral nerve. METHODS: We undertook a dose-response study to examine the impact of aging on resting NBF and its vasoreactivity to vasopressin. Nerve blood flow was measured using microelectrode hydrogen polarography. Arginine-vasopressin was administered both intra-arterially and topically. RESULTS: In young adult rats (two months old) topical epineurial application of arginine-vasopressin produced a concentration-dependent reduction of NBF (ED50 = 3.8 x 10(-5) mol/L). Intra-arterial arginine-vasopressin also reduced NBF. Nerve blood flow was lower in aged rats (12 months old) and less responsive to topically applied vasopressin. The aging group had significantly higher concentrations of vasopressin in plasma than did the younger group. CONCLUSIONS: The results suggest that vasopressin constricts vessels in peripheral nerve and that there is an age related decline in the vasoconstrictive response to vasopressin. There may be a reduction in receptor sensitivity in vascular smooth muscle cells in peripheral nerve with increasing age.

Aging↗

PubMed2002

[Significance of changes in individual indicators on intravascular homeostasis in development of circulatory hypoxia in aging].

The study comprised 45 healthy subjects aged 60-74. It was designed to examine the state of skin and bulbar microcirculation using the method of television capillaroscopy. The functional state of endothelial microvessels was studied with the help of laser doppler flowmeter by means of functional tests with postocclusion hyperaemia and intradermal injection of epinephrine solution in the dose of 0.1 ml (1.10-6 mol/l). The platelets aggregation activity was studied using the method of turbidimetry. The blood viscosity and functional state of erythrocytes were determined with the help of rotary viscosimeter at the shift velocity of 10 to 200s-1 with estimating the erythrocytes deformability and aggregation indexes. Oxygen saturation of the subcutaneous fat fibers was studied by polarography. It has been found that the increase of adrenalin-induction aggregation of platelets, the decrease of erythrocyte deformation and the endothelium synthesis disturbance caused relaxing factors play role in the circulatory hypoxia development.

Adult↗

PubMed2002

Calcium concentration in rat liver mitochondria during anoxic incubation.

BACKGROUND AND PURPOSE: The impairment of mitochondrial respiratory function is an important problem in anoxia-reoxygenation injury in animal cells. This study investigated the role of mitochondrial calcium ions (Ca2+) in a model of anoxic incubation in isolated rat liver mitochondria. METHODS: Mitochondria isolated from Wistar rat liver were subjected to anoxic incubation for 5 to 60 minutes. Changes in oxygen consumption by anoxic mitochondria were recorded using polarography. Changes in NAD(P)H fluorescence were recorded simultaneously. Intramitochondrial matrix free calcium concentration ([Ca2+]) was measured using the fluo-3/AM loading method. Respiratory function in anoxic mitochondria was measured polarographically from oxygen consumption. RESULTS: Mitochondrial state 3 respiration decreased progressively with increased duration of anoxic incubation, while state 4 respiration increased progressively. The decrease in the ADP/O ratio with the duration of anoxic incubation indicated that the efficiency of oxidative phosphorylation decreased with increased duration of anoxia. As the duration of anoxic incubation increased, the amplitude and rapidity of the oxido-reduction change in NAD(P)H fluorescence decreased. The respiratory control ratio showed that the functional integrity of mitochondria was linearly correlated with the free [Ca2+] in mitochondrial matrix (r2 = 0.977) and the total calcium concentration (r2 = 0.934). The free [Ca2+] in mitochondrial matrix significantly decreased with increasing anoxic duration. Total mitochondrial calcium concentration also decreased with increasing anoxic duration (p < 0.01). CONCLUSIONS: The supply of NADH was reduced during anoxic incubation of isolated rat hepatocyte mitochondria, which resulted in impairment of mitochondrial respiratory function. The decrease in free [Ca2+] in the mitochondrial matrix with increased duration of anoxic incubation implies that calcium ions may be released into the cytosol during anoxia.

Analysis of Variance↗

PubMed1975

The use of reference materials in the elemental analysis of biological samples.

Reference materials (RMs) are useful to compare the accuracy and precision of laboratories and techniques. The desirable properties of biological reference materials are listed, and the problems of production, homogenization and storage described. At present there are only 10 biological RMs available compared with 213 geological and 520 metallurgical RMs. There is a need for more biological RMs including special materials for microprobe analysis and for in vivo activation analysis. A study of 650 mean values for elements in RM Kale, analysed by many laboratories, leads to the following conclusions. 61% of the values lie within +/- 10% of the best mean, and 80% lie within +/- 20% of the best mean. Atomic absorption spectrometry gives results that are 5-30% high for seven elements, while instrumental neutron activation analysis gives low and imprecise results for K. Other techniques with poor interlaboratory precision include neutron activation for Mg, polarography for Zn and arc-spectrometry for many elements. More than half the values for elements in Kale were obtained by neutron activation, confirming the importance of this technique and the need for RMs. As a rough estimate, 6 X 10(9) elemental analyses of biological materials are carried out each year, mostly by medical, agricultural and food scientists. It seems likely that a substantial percentage of these are inaccurate, a situation that might be improved by quality control using standard RMs.

Chemistry Techniques, Analytical↗

PubMed1975

Development of analytical methods for the detection and determination of kynurenic and xanthurenic acids.

A survey was carried out on the techniques developed by numerous research workers in this important field since Liebig discovered the presence of kynurenic acid in the urine of dogs fed on meat and Musajo that of xanthurenic acid in the urine of rats on a fibrin diet. The survey starts with the old methods of assay by precipitation of kynurenic acid and goes on to include the more recent ones of colorimetric assay of xanthurenic acid with ferrous sulphate or ferric chloride and of kynurenic acid by means of transformation into a chloro-derivative of the type of Besthorn dyes. Chromatographic techniques including paper chromatography, thin-layer chromatography, column chromatography nad gas chromatography, enabled researchers to detect the slightest traces of the two quinolincarbonic acids in the biological fluids together with the other metabolites of tryptophan. Among the techniques adopted for this purpose electrophoresis, automatic analyzers, polarography and, finally, the use of labelled substances, in particular L-tryptophan-3-C14, are included.

Animals↗

PubMed2001

[Addition internal standard method in chromatographic quantitative analysis].

Internal standard method is a conventional chromatographic quantitative method which requires one or several internal standards added. The internal standard component must not be contained in the sample and need a good separation between the internal standard and sample components. In many cases selecting an internal standard is not convenient or even restricted by the seperation of components. In this paper, we try to combine the internal standard method and the addition method to form a new chromatographic quantitation method named addition internal standard method. The principles of addition internal standard method are suitable to not only chromatographic quantitation but also polarography etc. The related theory and foundation of the method are defined. The operation steps and the conditions suitable to the method are discussed. The advantages and disadvantages of this method are explained in detail.

Chromatography↗

PubMed2001

[Adsorptive voltammetric behavior of omeprazole and its application].

AIM: To study the electrochemical behavior of omeprazole (OPZ) and a new method for the determination of the compound was established by adsorptive stripping voltammetry. METHODS: Linear-sweep polarography and cyclic voltammetry were used. RESULTS: In a supporting electrolyte containing 0.1 mol.L-1 NH3-NH4Cl, a reduction peak of OPZ was observed by linear-sweep voltammetry at Hg electrode. The peak showed a potential of -1.04 V (vs Ag/AgCl at 100 mV.s-1) and adsorptive characteristics. The adsorbed species is most probably the neutral molecular of OPZ. The saturated adsorption of OPZ at Hg electrode is 9.55 x 10(-11) mol.cm-2 and every OPZ molecule occupies and area of 1.74 nm2. On the surface of the hanging mercury drop electrode, the adsorption of OPZ obeys Frumkin adsorption isotherm. The adsorption coefficient beta is 1.32 x 10(6), the Gibbs energy of adsorption delta G theta is -34.93 kJ.mol-1, the number of electrons transferred n is 4, the kinetics parameter alpha n alpha is 0.78, the rate constant of the surface electrode reaction ks is 0.18 s-1, the diffusion coefficient D of OPZ in solution is 1.03 x 10(-5) cm2.s-1. The detection limit of the adsorptive stripping voltammetry of OPZ is 2.0 x 10(-9) mol.L-1 under optimized condition. CONCLUSION: This indicates an irreversible process with adsorption.

Anti-Ulcer Agents↗

PubMed2003

[Study on pulmonary delivery of peptide drugs in rats: effects of absorption enhancers on cellular membrane fluidity].

AIM: To study the relationship between cellular membrane fluidity and relative bioavailability (Fr) of protein and peptide drugs combined with absorption enhancers after pulmonary administration in rats. METHODS: A series of model drug salmon calcitonin (sCT) solutions with 6 absorption enhancers (Brij78, sodium cholate, sodium caprylate, 2-hydroxypropyl-beta-cyclodextrin, lecithin and chitosan) were prepared and then delivered to rats by pulmonary route. Serum drug concentration was determined by radioimmunoassay method. Using the techniques of electron spin resonance and fluorescence polarography, the effects of enhancers on pulmonary cellular membrane fluidity were investigated. RESULTS: Fr values of sCT solution with some absorption enhancers (Brij78, sodium cholate, sodium caprylate, lecithin and chitosan) were significantly higher than those without enhancers. Brij78, lecithin and sodium caprylate, not only increased membrane lipid fluidity but also loosed the constitution of membrane protein. The effect of sodium cholate on membrane protein was low. Lipid fluidity was reduced and protein constitution was changed markedly, after pulmonary cellular membrane was treated by 0.5% chitosan solution. This result showed that the absorption enhancing of chitosan mainly came from its effects on membrane protein. Corresponded with lower Fr after pulmonary administration, 2-hydroxypropyl-beta-cyclodextrin (0.5% and 3%) had not significant effects on both lipid fluidity and protein constitution. CONCLUSION: The effects of enhancers on pulmonary absorption of peptide drugs in vivo might be investigated on the grounds of determination of cellular membrane fluidity in vitro.

Absorption↗

PubMed2004

Mitochondrial effects of antiretroviral therapies in asymptomatic patients.

BACKGROUND: A decrease in the mitochondrial (mt) DNA to nuclear DNA ratio has gained acceptance as a marker of mitochondrial toxicity in treated HIV-infected patients, but the functional meaning of this alteration is unclear. METHODS: We assessed mtDNA content, mitochondrial content and function in peripheral blood mononuclear cells (PBMCs) of consecutive asymptomatic HIV-infected patients. Patients selected had been receiving a first-line highly active antiretroviral therapy (HAART) regimen for at least 6 months, consisting of zidovudine plus lamivudine or stavudine plus didanosine plus either nelfinavir or nevirapine, or were antiretroviral-naive. The mtDNA content was assessed by quantitative real-time PCR, mitochondrial content by citrate synthase activity, enzyme activity of complexes III and IV (both partially encoded by mtDNA) of the electron transport chain by spectrophotometry, oxygen consumption by polarography, and oxidative damage in cell membranes by monitoring cis-parinaric acid fluorescence. RESULTS: Mitochondrial content was significantly lower in all treated groups. Patients receiving stavudine plus didanosine had mtDNA depletion and a decrease in complex IV activity. However, oxygen consumption capacity and lipid peroxidation were unaffected in all groups. CONCLUSION: Long-term HAART may induce mitochondrial abnormalities in PBMC mitochondria, which do not necessarily translate into functional abnormalities, at least in asymptomatic patients.

Adult↗

PubMed2004

[Morphologic and morphometric characteristics of the femoral head in experimental necrosis and after incomplete occlusion of the femoral artery].

Partial occlusion (by 70-80%) of the femoral artery (FA) below its bifurcation with the deep femoral one was created in 15 dogs 6 months after modeling of aseptic necrosis of femoral head (FH). The dynamics of local circulation was evaluated using the methods of hydrogen clearance, angiography, flowmetry, polarography and mingography. FA and neighboring vessels as well as FH bone tissue were studied using histological, histochemical and morphometric methods. It was found that partial occlusion of FA below its bifurcation with the deep femoral branch resulted after 180-240 days in a redistribution of blood flow in favor of the latter along with a formation of collateral vessel widening as well as in the change in the circulation vector in the direction of the hip joint. This contributed to FH revascularization after modeling of its traumatic aseptic necrosis. The results of the morphological analysis indicate the activation of osteogenesis and gradual replacement of the necrotic area in FH with a newly formed osseous tissue and are suggestive of possible application of this method for clinical use.

Animals↗

PubMedDate not supplied

[The effect of intermittent normobaric hypoxia on oxygen metabolism in hypertonic pilots].

Oxygen tissue metabolism was evaluated in hypertonic pilots in order to draw up an optimal treatment plan. Oxygen metabolism kinetics was determined with the help of transcutaneous polarography and the local ischemic extremity test was applied to measure the O2 utilization efficiency. Breathing mixture of 90% nitrogen and 10% oxygen (GGS-10) was used in therapeutic sessions of intermittent normobaric hypoxia. Results point to the reduced tissue breathing intensity and cell functional energy reserve in hypertonic patients. However, O2 metabolism is much closer to normal in pilots as compared with non-flyers. In pilots, O2 utilization is more intensive, energy supply of cells is higher, O2 transport and utilization are well-balanced, and tissue breathing is less reactive to the hypoxic factor. Dynamic kinetics of O2 metabolism tested post treatment suggested activation of O2 tissue metabolism in the hypertonic pilots rather than O2 transport which was stimulated in non-flyers. In addition, by the end of treatment the pilots were advised to extend the period of breathing GGS-10 leaving the period of air breathing unchanged. Consequently, the pilots were more adaptable to hypoxia than the non-flyers and, therefore, improved O2 tissue metabolism more rapidly.

Adaptation, Physiological↗